The goal of this project is to characterize the mechanisms by which anti-idiotype antibodies regulate immune responses and lymphocyte function. A system has been developed in which, for the first time, soluble antibody responses to the synthetic polytide (T,G)-A--L can be generated and detected in vitro using antigenrimed lymph node cells. Responses are antigen dependent and specific, and H-2inked Ir gene regulated. Antibodies specific for the idiotypes of anti-(T,G)--L antibodies induce antigen-independenet anti-(T,G)-A--L antibody response. These responses are specific at the levels of the anti-idiotype reagent, the antigen-priming, and the antibody produced. The anti-idiotype antibodies stimulate function from antigen-primed T lymphocytes in the form of soluble helper lymphokines, and function from both primed and unprimed B cells in the form of specific antibody secretion. Unprimed B cells, in addition to anti-idiotype, requires either primed T cells or idiotype or unrelated antibody complexes to be present in order to obtain function. Responses to anti-idiotype antibodies, in contrast to those to antigen, appear not to be regulated by Ir genes. A monoclonal anti-idiotype which reacts with a public idiotope present on the majority of anti-(T,G)-A--L antibodies has been obtained, and is being evaluated for functional effects.